Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction
(1) Background: Numerous prions exist in the budding yeast, including [<i>SWI</i><sup>+</sup>], the prion form of Swi1—a subunit of the chromatin-remodeling complex SWI/SNF. Despite decades of research, the molecular mechanisms underlying prion initiation and propagation are...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/7/1366 |
| _version_ | 1797433041251991552 |
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| author | Zhiqiang Du Brandon Cho Liming Li |
| author_facet | Zhiqiang Du Brandon Cho Liming Li |
| author_sort | Zhiqiang Du |
| collection | DOAJ |
| description | (1) Background: Numerous prions exist in the budding yeast, including [<i>SWI</i><sup>+</sup>], the prion form of Swi1—a subunit of the chromatin-remodeling complex SWI/SNF. Despite decades of research, the molecular mechanisms underlying prion initiation and propagation are not fully understood. In this study, we aimed to identify endogenous cellular proteins that destabilize [<i>SWI</i><sup>+</sup>]. (2) Methods: We screened the MoBY-ORF 2.0 library for proteins that destabilize [<i>SWI</i><sup>+</sup>] upon overproduction. We further explored the effects of the identified candidates against other yeast prions and analyzed their potential prion-curing mechanisms. (3) Results: Eighty-two [<i>SWI</i><sup>+</sup>] suppressors were identified, and their effects were shown to be [<i>SWI</i><sup>+</sup>]-specific. Interestingly, a few documented [<i>SWI</i><sup>+</sup>] suppressors were not among the identified hits. Further experiments indicate that, for some of these [<i>SWI</i><sup>+</sup>] suppressors, their overproduction, and thus their prion-curing activities, are regulated by environmental conditions. Bioinformatics analyses show that our identified [<i>SWI</i><sup>+</sup>] suppressors are involved in diverse biological functions, with gene ontology term enrichments specifically for transcriptional regulation and translation. Competition for Swi1 monomers between [<i>SWI</i><sup>+</sup>] and Swi1 interactors, including the SWI/SNF complex, is a potential prion-curing mechanism. (4) Conclusions: We identified a number of [<i>SWI</i><sup>+</sup>]-specific suppressors that highlight unique features of [<i>SWI</i><sup>+</sup>] in maintaining its self-perpetuating conformations. |
| first_indexed | 2024-03-09T10:10:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T10:10:24Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-621ea7705a3c45e1a2c6cd3d240d9e1d2023-12-01T22:46:50ZengMDPI AGViruses1999-49152022-06-01147136610.3390/v14071366Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon OverproductionZhiqiang Du0Brandon Cho1Liming Li2Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA(1) Background: Numerous prions exist in the budding yeast, including [<i>SWI</i><sup>+</sup>], the prion form of Swi1—a subunit of the chromatin-remodeling complex SWI/SNF. Despite decades of research, the molecular mechanisms underlying prion initiation and propagation are not fully understood. In this study, we aimed to identify endogenous cellular proteins that destabilize [<i>SWI</i><sup>+</sup>]. (2) Methods: We screened the MoBY-ORF 2.0 library for proteins that destabilize [<i>SWI</i><sup>+</sup>] upon overproduction. We further explored the effects of the identified candidates against other yeast prions and analyzed their potential prion-curing mechanisms. (3) Results: Eighty-two [<i>SWI</i><sup>+</sup>] suppressors were identified, and their effects were shown to be [<i>SWI</i><sup>+</sup>]-specific. Interestingly, a few documented [<i>SWI</i><sup>+</sup>] suppressors were not among the identified hits. Further experiments indicate that, for some of these [<i>SWI</i><sup>+</sup>] suppressors, their overproduction, and thus their prion-curing activities, are regulated by environmental conditions. Bioinformatics analyses show that our identified [<i>SWI</i><sup>+</sup>] suppressors are involved in diverse biological functions, with gene ontology term enrichments specifically for transcriptional regulation and translation. Competition for Swi1 monomers between [<i>SWI</i><sup>+</sup>] and Swi1 interactors, including the SWI/SNF complex, is a potential prion-curing mechanism. (4) Conclusions: We identified a number of [<i>SWI</i><sup>+</sup>]-specific suppressors that highlight unique features of [<i>SWI</i><sup>+</sup>] in maintaining its self-perpetuating conformations.https://www.mdpi.com/1999-4915/14/7/1366protein aggregationprion propagationprion inhibitorsSwi1[<i>SWI</i><sup>+</sup>]SWI/SNF |
| spellingShingle | Zhiqiang Du Brandon Cho Liming Li Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction Viruses protein aggregation prion propagation prion inhibitors Swi1 [<i>SWI</i><sup>+</sup>] SWI/SNF |
| title | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
| title_full | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
| title_fullStr | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
| title_full_unstemmed | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
| title_short | Identifying Endogenous Cellular Proteins Destabilizing the Propagation of Swi1 Prion upon Overproduction |
| title_sort | identifying endogenous cellular proteins destabilizing the propagation of swi1 prion upon overproduction |
| topic | protein aggregation prion propagation prion inhibitors Swi1 [<i>SWI</i><sup>+</sup>] SWI/SNF |
| url | https://www.mdpi.com/1999-4915/14/7/1366 |
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